Journal Article

DZNE-2021-00783

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Ecto-GPR37: a potential biomarker for Parkinson's disease.

Morató, X. ; Garcia-Esparcia, P. ; Argerich, J. ; Llorens Torres, F. J.Extern* ; Zerr, I.DZNE* ; Paslawski, W. ; Borràs, E. ; Sabidó, E. ; Petäjä-Repo, U. E. ; Fernández-Dueñas, V. ; Ferrer, I. ; Svenningsson, P. ; Ciruela, F.

2021
Biomed Central London

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Please use a persistent id in citations: doi:10.1186/s40035-021-00232-7

Abstract: α-Synuclein has been studied as a potential biomarker for Parkinson's disease (PD) with no concluding results. Accordingly, there is an urgent need to find out reliable specific biomarkers for PD. GPR37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile parkinsonism. Here, we investigated whether GPR37 is upregulated in sporadic PD, and thus a suitable potential biomarker for PD.GPR37 protein density and mRNA expression in postmortem substantia nigra (SN) from PD patients were analysed by immunoblot and RT-qPCR, respectively. The presence of peptides from the N-terminus-cleaved domain of GPR37 (i.e. ecto-GPR37) in human cerebrospinal fluid (CSF) was determined by liquid chromatography-mass spectrometric analysis. An engineered in-house nanoluciferase-based immunoassay was used to quantify ecto-GPR37 in CSF samples from neurological control (NC) subjects, PD patients and Alzheimer's disease (AD) patients.GPR37 protein density and mRNA expression were significantly augmented in sporadic PD. Increased amounts of ecto-GPR37 peptides in the CSF samples from PD patients were identified by mass spectrometry and quantified by the in-house ELISA method. However, the CSF total α-synuclein level in PD patients did not differ from that in NC subjects. Similarly, the cortical GPR37 mRNA expression and CSF ecto-GPR37 levels in AD patients were also unaltered.GPR37 expression is increased in SN of sporadic PD patients. The ecto-GPR37 peptides are significantly increased in the CSF of PD patients, but not in AD patients. These results open perspectives and encourage further clinical studies to confirm the validity and utility of ecto-GPR37 as a potential PD biomarker.

Keyword(s): Aged (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Biomarkers (MeSH) ; Brain Chemistry (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Parkinson Disease: diagnosis (MeSH) ; RNA, Messenger: biosynthesis (MeSH) ; Receptors, G-Protein-Coupled: analysis (MeSH) ; Receptors, G-Protein-Coupled: biosynthesis (MeSH) ; Receptors, G-Protein-Coupled: genetics (MeSH) ; Reproducibility of Results (MeSH) ; Substantia Nigra: metabolism (MeSH) ; Up-Regulation (MeSH) ; alpha-Synuclein: cerebrospinal fluid (MeSH) ; Alzheimer’s disease ; Biomarker ; Cerebrospinal fluid ; GPR37 ; Orphan receptor ; Pael-R ; Parkinson’s disease ; α-Synuclein

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Contributing Institute(s):

1. Translational Studies and Biomarker (AG Zerr)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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